Oil-filled polymer microcapsules for ultrasound-mediated delivery of lipophilic drugs.
The use of ultrasound contrast agents as local drug delivery systems continues to grow. Current limitations are the amount of drug that can be incorporated as well as the efficiency of drug release upon insonification. This study focuses on the synthesis and characterisation of novel polymeric microcapsules for ultrasound-triggered delivery of lipophilic drugs. Microcapsules with a shell of fluorinated end-capped poly(L-lactic acid) were made through pre-mix membrane emulsification and contained, apart from a gaseous phase, different amounts of hexadecane oil as a drug-carrier reservoir. Mean number weighted diameters were between 1.22 microm and 1.31 microm. High-speed imaging at approximately 10 million fames per second showed that for low acoustic pressures (1 MHz, 0.24 MPa) microcapsules compressed but remained intact. At higher diagnostic pressures of 0.51 MPa, microcapsules cracked, thereby releasing the encapsulated gas and model lipophilic drug. Using conventional ultrasound B-mode imaging at a frequency of 2.5 MHz, a marked enhancement of scatter intensity over a tissue-mimicking phantom was observed for all differently loaded microcapsules. The partially oil-filled microcapsules with high drug loads and well-defined acoustic activation thresholds have great potential for ultrasound-triggered local delivery of lipophilic drugs under ultrasound image-guidance.
Kooiman
Klazina
K
Department of Biomedical Engineering, Erasmus MC, Rotterdam, The Netherlands. k.kooiman@erasmusmc.nl
Böhmer
Marcel R
MR
Emmer
Marcia
M
Vos
Hendrik J
HJ
Chlon
Ceciel
C
Shi
William T
WT
Hall
Christopher S
CS
de Winter
Suzanne H P M
SH
Schroën
Karin
K
Versluis
Michel
M
de Jong
Nico
N
van Wamel
Annemieke
A
D000473:Alkanes / Q000032:analysis / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002214:Capsules; D043822:Cyclodecanes / Q000032:analysis / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D005466:Fluorocarbons / Q000737:chemistry; D008401:Gas Chromatography-Mass Spectrometry; D005740:Gases / Q000032:analysis / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D019344:Lactic Acid / Q000737:chemistry; D008854:Microscopy, Electron; D010316:Particle Size; D019047:Phantoms, Imaging; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000737:chemistry; D011091:Polyesters; D011108:Polymers / Q000737:chemistry; D011142:Polyvinyl Alcohol / Q000737:chemistry; D013499:Surface Properties; D014465:Ultrasonics; D014463:Ultrasonography
D000473:Alkanes; D002214:Capsules; D043822:Cyclodecanes; D005466:Fluorocarbons; D005740:Gases; D004364:Pharmaceutical Preparations; D011091:Polyesters; D011108:Polymers; D019344:Lactic Acid; C033616:poly(lactide); D011142:Polyvinyl Alcohol; C007932:n-hexadecane